基于网络药理学探讨大黄黄连泻心汤治疗脓毒症心肌抑制的作用机制

The Mechanism of Dahuang Huanglian Xiexin Decoction in Treating Sepsis-induced Myocardial Dysfunction Based on Network Pharmacology

目的运用网络药理学方法探究大黄黄连泻心汤治疗脓毒血症心肌抑制(SIMD)的分子生物学机制。方法通过中药系统药理学数据库及分析平台(TCMSP)筛选大黄黄连泻心汤的有效成分及潜在靶点,利用Genecards、OMIM数据库获取SIMD的相关靶点基因,并借助PALM-IST对PubMed数据库进行文本挖掘作为疾病靶点的补充。采用Cytoscape 3.7.2软件构建大黄黄连泻心汤治疗SIMD的药物-成分-靶点网络关系图。通过STRING平台构建蛋白互作网络。运用R 3.6.2软件对预测靶标进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。结果获得大黄黄连泻心汤治疗SIMD的有效成分15个、相关靶点99个,其中槲皮素、β-谷甾醇、巴马汀、芦荟大黄素等为关键成分,通过调控NOS2、PTGS2、JUN、CASP3、BCL2、CASP8、CASP9、IL1B等靶点,干预肿瘤坏死因子(TNF)信号通路、糖尿病并发症中的AEG-RAGE信号通路、白细胞介素-17(IL-17)等信号通路,调控氧化、凋亡、炎症反应等生物过程发挥治疗作用。结论大黄黄连泻心汤多成分具有多靶点、多途径协同治疗脓毒血症心肌抑制的作用特点,为大黄黄连泻心汤在SIMD的临床治疗靶点以及实验研究提供方向。

Objective To explore the molecular biology mechanism of Dahuang Huanglian Xiexin Decoction in the treatment of sepsis-induced myocardial dysfunction(SIMD)by network pharmacology.Methods The active components and potential targets of Dahuang Huanglian Xiexin Decoction were filtrated from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),SIMD related targets were gained by Genecards,OMIM databases,and PALM-IST platform was used to literature mining from PubMed database.The"drug-component-target"interaction network was constructed by Cytoscape 3.7.2 software.STRING platform was used to build protein-protein interaction network and R 3.6.2 software was used to carry out the GO enrichment and KEGG enrichment analysis of candidate targets.Results There were 15 active components,mainly consist of quercetin,beta-sitosterol,palmatine,aloe-emodin,and 99 candidate targets in Dahuang Huanglian Xiexin Decoction acting on SIMD.Those ingredients plaIied a therapeutic role by regulating NOS2,PTGS2,JUN,CASP3,BCL2,CASP8,CASP9,IL1B and other targets to interfere signaling pathway such as tumor necrosis factor(TNF)signaling pathway,AEG-RAGE signaling pathway in diabetic complications,and IL-17 signaling pathway,and biological processes such as oxidation,apoptosis,and inflammation.Conclusion Dahuang Huanglian Xiexin Decoction with the characteristics of multi-component,multi-target,and multi-channel synergistic treatment of sepsis myocardial inhibition.Might be the basis for the clinical therapeutic target and experimental research.